Adjuvant activities of immunostimulating natural products: Astragalus membranaceus (Fisch.) Bge and Coriolus versicolor in BNT162b2 vaccination against COVID-19 infection.

The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been developing all over the world for more than three years. In late 2020, several variants of concern (VOC) of SARS-CoV-2 virus emerged, with increased viral fitness and transmissibility by mutations of the spike proteins of the viral particle, denting hopes that the use of early-generation vaccines for a widespread protective immunity against viral infection. The use of adjuvant may enhance the immune responses of the conventional application of the COVID-19 vaccine. We have shown that the water extract of two beta-glucan enriched immunostimulating natural products: Astragalus membranaceus (Fisch.) Bge (AM) and Coriolus versicolor (CV) could induce innate immunity-related cytokines from human monocytes (CCL5, IL-6, IL-10 and TNF-α) and monocyte-derived dendritic cells (IL-1β, IL-10, IL-12 and TNF-α). Using BALB/c mice, orally administrated AM and CV (1384 and 742 mg/kg/day) for 4 days after vaccination, respectively, could enhance (1) the IgG binding activities of BNT162b2 vaccination against ancestral and Delta SARS-CoV-2 spike proteins by 5.8 and 4.3 folds, respectively, (2) the IgG3 subclass production of BNT162b2 vaccination against ancestral and variant SARS-CoV-2 spike proteins, and (3) the in vitro antibody neutralizing activities of BNT162b2 vaccinated mice. In conclusion, combining AM and CV was effective in acting as an oral adjuvant with the mRNA vaccine BNT162b2 to improve the antigen binding activities against SARS-CoV-2 ancestral and variant SARS-CoV-2 spike proteins, probably via trained immunity of macrophages and dendritic cells.